Molecular diagnosis and clinical onset of CMT in Japan

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J Hum Genet. 2011 Feb 17. [Epub ahead of print]

Molecular diagnosis and clinical onset of Charcot-Marie-Tooth disease in Japan.

Abe A, Numakura C, Kijima K, Hayashi M, Hashimoto T, Hayasaka K.

Department of Pediatrics, Yamagata University School of Medicine, Yamagata,

Japan.

Abstract

To study the genetic background of Japanese Charcot-Marie-Tooth disease (CMT)

patients, we analyzed qualitative and quantitative changes in the

disease-causing genes mainly by denaturing high performance liquid

chromatography and multiplex ligation-dependent probe analysis in 227 patients

with demyelinating CMT and 127 patients with axonal CMT.

In demyelinating CMT, we identified 53 patients with PMP22 duplication, 10

patients with PMP22 mutations, 20 patients with MPZ mutations, eight patients

with NEFL mutations, 19 patients with GJB1 mutations, one patient with EGR2

mutation, five patients with PRX mutations and no mutations in 111 patients.

In axonal CMT, we found 14 patients with MFN2 mutations, one patient with GARS

mutation, five patients with MPZ mutations, one patient with GDAP1 mutation, six

patients with GJB1 mutations and no mutations in 100 patients.

Most of the patients carrying PMP22, MPZ, NEFL, PRX and MFN2 mutations showed

early onset, whereas half of the patients carrying PMP22 duplication and all

patients with GJB1 or MPZ mutations showing axonal phenotype were adult onset.

Our data showed that a low prevalence of PMP22 duplication and high frequency of

an unknown cause are features of Japanese CMT. Low prevalence of PMP22

duplication is likely associated with the mild symptoms due to genetic and/or

epigenetic modifying factors.

Journal of Human Genetics advance online publication, 17 February 2011;

doi:10.1038/jhg.2011.20